Persistent H. pylori colonization in early acquisition age of mice related with higher gastric sialylated Lewis x, IL-10, but lower interferon-γ expressions

<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection is less prevalent in childhood. This study validated whether the rates of <it>H. pylori </it>colonization depend on different acquisition ages, and correlate with the different gastric Lewis antigens or cytokine expressions after <it>H. pylori </it>acquisition.</p> <p>Methods</p> <p>We applied a young (7-day-old) C57BL/6 mice group (n = 50) and adult (6-week-old) C57BL/6 mice group (n = 50). In each group, 30 mice were challenged with <it>H. pylori </it>and 20 mice served as naïve control. The success of <it>H. pylori </it>colonization was assessed on the 2^ndweek and the 8^thweek, respectively. The intensity of the Lewis x, sialylated Lewis x<sup/>(sialyl-Le^x), and cytokine expressions, including TNF-α, IFN-γ, IL-6, IL-10, and IL-1β, were immunochemically stained and graded.</p> <p>Results</p> <p>On the 2^ndweek after <it>H. pylori </it>challenge, the colonization rates of <it>H. pylori </it>were similar between the young mice group and the adult mice group (89% vs. 100%, <it>P </it>> 0.05). However, on the 8^thweek, the <it>H. pylori </it>colonization rate was significantly lower in the young mice group than in the adult mice group (53% vs. 95%, <it>P </it>= 0.003). On the 8^thweek, the young mice with a persistence of <it>H. pylori </it>colonization had higher sialyl-Le^x, higher IL-10, and lower IFN-γ than those of the mice that lost colonization during the 2^ndto the 8^thweek (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>The persistence of <it>H. pylori </it>colonization could be an acquisition-age determinant process. After <it>H. pylori </it>exposure at an early acquisition age, the host response with a higher sialyl-Le^xand IL-10, but a lower IFN-γ correlates to the consequent persistence of <it>H. pylori </it>colonization.</p

Etiology and Treatment of Childhood Peptic Ulcer Disease in Taiwan: A Single Center 9-Year Experience

Background/PurposePeptic ulcer disease (PUD) in children is relatively rare as compared with adults. This study aimed to assess the etiology, clinical and histological characteristics, and treatment of PUD in children.MethodsAll children aged < 18 years with an endoscopic diagnosis of PUD were enrolled in a tertiary referral center. The demographic data, clinical, endoscopic, and histological findings were compared between patients with different causes of PUD.ResultsFrom 1234 endoscopic examinations, 67 (5.4%) children (median age, 11.4 years) with gastric ulcer (GU; n = 27) or duodenal ulcer (DU; n = 40) were included. Thirty-two (47.7%) of them had Helicobacter pylori infection and 11 (16.5%) had previous use of non-steroidal anti-inflammatory drugs (NSAIDs). Non-H. pylori, non-NSAID PUD was found in 24 (35.8%) patients. Children with H. pylori-related PUD had a significantly higher mean age, antral chronic inflammatory score, rate of familial PUD, and presence of DU and nodular gastritis than those with NSAID-related and non-H. pylori, non-NSAID PUD (p < 0.01). In contrast, children with NSAID-related PUD had a higher rate of upper gastrointestinal bleeding, associated with acute febrile disease, than those with H. pylori-related and non-H. pylori, non-NSAID PUD (p < 0.05). All but two patients with non-H. pylori, non-NSAID PUD were disease free after H. pylori eradication and proton pump inhibitor treatment for 1–2 months.ConclusionIn children, H. pylori-related PUD is associated with familial peptic ulcer and the presence of DU. However, short-term NSAID use is correlated highly with GU. The outcome of childhood PUD is good

Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways

<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve <it>H. pylori</it>-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.</p> <p>Results</p> <p>Challenge with <it>H. pylori </it>increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after <it>H. pylori </it>infection in a dose-dependent manner. A higher dose (MOI 100) of <it>L. acidophilus </it>pre-treatment attenuated the <it>H. pylori</it>-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. <it>L. acidophilus </it>also inhibited <it>H. pylori</it>-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. <it>L. acidophilus </it>pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting.</p> <p>Conclusions</p> <p><it>H. pylori </it>infection induces Smad7, NFκB, IL-8, and TNF-α production <it>in vitro</it>. Higher doses of <it>L. acidophilus </it>pre-treatment reduce <it>H. pylori</it>-induced inflammation through the inactivation of the Smad7 and NFκB pathways.</p

Matrix metalloproteinase-3 promoter polymorphisms but not dupA-H. pylori correlate to duodenal ulcers in H. pylori-infected females

<p>Abstract</p> <p>Background</p> <p>This study investigated if the <it>H. pylori dupA </it>genotype and certain host single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), including MMP-3, MMP-7, MMP-9, TIMP-1 and TIMP-2, might correlate with ulcer risk of <it>H. pylori-</it>infected Taiwanese patients.</p> <p>Results</p> <p>Of the 549 <it>H. pylori-</it>infected patients enrolled, 470 patients (265 with gastritis, 118 with duodenal ulcer, and 87 with gastric ulcer) received SNPs analysis of MMP-3_{-1612 6A > 5A}, MMP-7_{-181 A > G}, MMP-9_{exon 6 A > G}, TIMP-1_{372 T > C}and TIMP-2_{-418 G > C}by PCR-RFLP. The 181 collected <it>H. pylori </it>isolates were detected for the <it>dupA </it>genotype by PCR. The rates of <it>dupA</it>-positive <it>H. pylori </it>infection were similar among patients with duodenal ulcer (22.8%), gastric ulcer (20.0%), and gastritis (25.5%) (<it>p </it>> 0.05). Males had higher rates of duodenal ulcer and gastric ulcer than females (<it>p </it>< 0.01). Of <it>H. pylori</it>-infected patients, the MMP-3 6A6A genotype were more common in patients with duodenal ulcers than in those with gastritis (87.7% <it>vs</it>. 74.9%, <it>p </it>< 0.05) in females. This genotype had a 2.4-fold (95% CI: 1.02-5.66) increased risk of duodenal ulcer, compared to those with the 5A carrier. Combining the MMP-3/TIMP-1 genotype as 6A6A/CC, the risk of duodenal ulcer increased up to 3.6 fold (<it>p </it>< 0.05) in <it>H. pylori-</it>infected females.</p> <p>Conclusions</p> <p>The MMP-3 promoter polymorphism, but not the <it>dupA</it>-status, may correlate with susceptibility to duodenal ulcer after <it>H. pylori </it>infection in Taiwanese females.</p

Helicobacter pylori with stronger intensity of CagA phosphorylation lead to an increased risk of gastric intestinal metaplasia and cancer

<p>Abstract</p> <p>Background</p> <p>Nearly all Taiwanese <it>H. pylori </it>stains are <it>cagA</it>-genopositive and encode CagA protein. In this study, we evaluated whether different intensity of tyrosine phosphorylated-CagA (p-CagA) had an impact on the clinical diseases and histological outcomes in this area.</p> <p>Results</p> <p>We enrolled 469 dyspeptic patients and prospectively obtained the gastric biopsy specimens and the <it>H. pylori </it>isolates. These patients were categorized according to the clinical diseases, such as duodenal ulcer, gastric ulcer, gastric cancer, and gastritis with or without intestinal metaplasia. Their gastric specimens were reviewed by the updated Sydney's system. Furthermore, a total of 146 patients were randomly selected from each clinical category for evaluation of their isolates' p-CagA intensity by <it>in vitro </it>AGS cells co-culture. The p-CagA was sparse in 30 (20.5%), weak in 59 (40.5%), and strong in 57 (39%) isolates. The isolates from the patients of gastric cancer or gastritis with intestinal metaplasia had stronger p-CagA intensity than those of gastritis without intestinal metaplasia (<it>p </it>≤ 0.002). Moreover, the patients infected with isolates with strong or weak p-CagA intensity had a higher risk of gastric intestinal metaplasia (<it>p </it>< 0.05, odds ratio 3.09~15.26) than those infected with sparse p-CagA isolates.</p> <p>Conclusions</p> <p>Infection with <it>H. pylori </it>stains with stronger p-CagA intensity may lead to an increased risk of gastric intestinal metaplasia and cancer.</p

Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Srcdependent nuclear factor-

ABSTRACT Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n ϭ 20), gastric ulcer (HU, n ϭ 20), duodenal ulcer (HD, n ϭ 21), and gastric cancer (HC, n ϭ 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3Ј repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-B, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-B activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pyloriinduced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression

Weak up-regulation of serum response factor in gastric ulcers in patients with co-morbidities is associated with increased risk of recurrent bleeding

<p>Abstract</p> <p>Background</p> <p>Serum response factor (SRF) is crucial for gastric ulcer healing process. The study determined if gastric ulcer tissues up-regulate SRF and if such up-regulation correlated with co-morbidities and the risk of recurrent bleeding.</p> <p>Methods</p> <p>Ulcer and non-ulcer tissues were obtained from 142 patients with active gastric ulcers for SRF expression assessed by immunohistochemistry. Based on the degree of SRF expression between these two tissue types, SRF up-regulation was classified as strong, intermediate, and weak patterns. The patients were followed-up to determine if SRF up-regulation correlated to recurrent bleeding.</p> <p>Results</p> <p>Gastric ulcer tissues had higher SRF expression than non-ulcer tissues (<it>p </it>< 0.05). Patients with strong SRF up-regulation had lower rates of stigmata of recent hemorrhage (SRH) on the ulcer base than the others (<it>p </it>< 0.05). Multivariate logistic regression confirmed that co-morbidities and weak SRF up-regulation were two independent factors of recurrent gastric ulcer bleeding (<it>p </it>< 0.05). Combining both factors, there was an 8.29-fold (95% CI, 1.31~52.62; <it>p </it>= 0.03) higher risk of recurrent gastric ulcer bleeding.</p> <p>Conclusions</p> <p>SRF expression is higher in gastric ulcer tissues than in non-ulcer tissues. Weak SRF up-regulation, combined with the presence of co-morbidities, increase the risk of the recurrent gastric ulcer bleeding.</p

Clinical Application of 20 Mhz Endosonography and Anti-Helicobacter Pylori Immunoblots to Predict Regression of Low-Grade Gastric Maltoma by H -Pylori Eradication

Aim. We tested whether serial 20 MHz endosonography (EUS) and anti- Helicobacter pylori immunoblots can predict the complete regression of gastric MALToma by H. pylori eradication. Methods. The serums of 17 MALToma patients, including 15 with low grade and two with high grade, were collected before therapy. Fifteen patients with low-grade MALToma and 18 nonMALToma patients, all infected with H. pylori , have been followed with serum sampling, endoscopy, and EUS on enrollment, on the 2nd, 6th, and 12th months after anti-H. pylori therapy. All sera were tested for anti- H. pylori immunoblots, including 19.5, 26.5, 30, 35, 89, 116 KDa ( CagA), FldA. The DNAs were extracted serially from the biopsy of MALToma patients before and after therapy to perform polymerase chain reaction ( PCR) for the immunoglobulin heavy-chain gene monoclonality. Results. MALToma patients had higher prevalence rates of anti-FldA protein, 19.5 and 30 KDa antibodies of H. pylori (p 0.05). Complete regression of MALToma was observed in 73.3% ( 11/15) of patients. Evaluation with 20 MHz EUS, for the initial tumor depth and its normalization on the 6th month had 90.9% sensitivity and 100 % specificity to predict the complete regression. Discussion. The negative seroconversions of the smaller-molecular-weight proteins, but not CagA and FldA, correlate with regression of MALToma by H. pylori eradication. 20 MHz EUS can effectively predict the therapeutic response of MALToma